Continuous low irradiance photodynamic therapy system and method

ABSTRACT

Systems and methods are providing for treating a patient with continuous low irradiance photodynamic therapy. A disclosed method includes applying a photosensitizer to the patient; applying a conformable skin facing light applicator to the patient; and providing continuous low irradiance photodynamic therapy through the light applicator. A disclosed system includes a light applicator having a fiber optic cloth. The light applicator is conformable so that it can be worn against a patient&#39;s skin and the fiber optic cloth has a two dimensional surface that emits light in a direction toward a patient&#39;s skin. In this aspect, the power of the light emitted from the two dimensional surface in a direction toward a patient&#39;s skin is less than or equal to about 5 mW/cm 2 .

BACKGROUND OF THE INVENTION

Photodynamic therapy (PDT) is a ternary treatment for cancer involvingthree key components: a photosensitizer drug, light, and tissue oxygen.It is also being used for treatment of psoriasis and acne, among otherskin growths and is an approved treatment for wet macular degeneration.

In photodynamic therapy, either a photosensitizer or the metabolicprecursor of one is administered to the patient. A photosensitizer is achemical compound that can be excited by light of a specific wavelength.This excitation uses visible or near-infrared light. The tissue to betreated is exposed to light suitable for exciting the photosensitizer.Usually, the photosensitizer is excited from a ground singlet state toan excited singlet state. It then undergoes intersystem crossing to alonger-lived excited triplet state. One of the few chemical speciespresent in tissue with a ground triplet state is molecular oxygen. Whenthe photosensitizer and an oxygen molecule are in close proximity, anenergy transfer can take place that allows the photosensitizer to relaxto its ground singlet state, and create an excited singlet state oxygenmolecule. Singlet oxygen is a very aggressive chemical species and willvery rapidly react with any nearby biomolecules. (The specific targetsdepend heavily on the photosensitizer chosen.) Ultimately, thesedestructive reactions will result in cell killing through apoptosis ornecrosis.

Photodynamic therapy is delivered as an acute therapy comprising asingle drug and light administration, or in a series of administrationsover time (usually with months between PDT sessions). More recently, theconcept of metronomic PDT (“mPDT”) has been introduced. In mPDT, thedrug and/or light are delivered either in multiple pulses orcontinuously such that the ‘fractions’ overlap pharmacokinetically andphotobiologically. (See, e.g., Stuart K. Bisland et al., “Metronomicphotodynamic therapy: A novel approach to treating brain tumours,”Ontario Cancer Institute and Dept. of Medical Biophysics, University ofToronto, presented at the OPTO Canada meeting in Ottawa; 9 May 2002; andStuart K. Bisland et al., “Metronomic Photodynamic Therapy as a NewParadigm for Photodynamic Therapy: Rationale and Preclinical Evaluationof Technical Feasibility for Treating Malignant Brain Tumors,”Photochemistry and Photobiology (July/August 2004), each of which isincorporated by reference in its entirety).

Despite these advances however, at least two important challenges remainin providing effective low dose therapy: (1) delivery of light to thetarget tissue over an extended period in a manner that providesconsistent energy delivery to what can be an uneven surface contour; and(2) delivery of light to the target tissue over an extended period in amanner that will be acceptable to patients over this time.

BRIEF SUMMARY OF THE INVENTION

The present invention is directed to systems and methods for providingcontinuous low irradiance photodynamic therapy to a patient. The methodsand systems of the invention are most likely to be applicable topatients with conditions that may be amenable to treatment usingconventional photodynamic therapy, but the invention enables treatmentsthat are less damaging to the patient and that may be provided in waysthat can be comfortable and convenient for the patient. In one aspect,the invention includes a method for providing continuous low irradiancephotodynamic therapy to a patient. The method includes applying aphotosensitizer to the patient; applying a conformable skin facing lightapplicator to the patient; and providing continuous low irradiancephotodynamic therapy through the light applicator.

In specific embodiments of this aspect of the invention, the lightapplicator can include a fiber optic cloth and the light applicator canprovide a light intensity to the patient of less than or equal to about5 mW/cm². Embodiments of the method of this aspect can also include, forexample, 5-aminolevulinic acid as the photosensitizer, and thephotosensitizer can be administered orally. In still further specificembodiments, the method can be applied to treat a disease of the skin, askin or soft tissue cancer, skin metastases of a malignant melanoma orchest wall progression of breast cancer in the patient, or small jointarthritis.

In a further aspect, the invention includes a system for providingcontinuous low irradiance photodynamic therapy. The system includes alight applicator having a fiber optic cloth. The light applicator isconformable so that it can be worn against a patient's skin and thefiber optic cloth has a two dimensional surface that emits light in adirection toward a patient's skin. In this aspect, the power of thelight emitted from the two dimensional surface in a direction toward apatient's skin is less than or equal to about 5 mW/cm².

In further specific embodiments of the various aspects of the invention,the light applicator can provide a light intensity to the patient ofbetween about 0.25 and 3 mW/cm². The light applicator can also beapplied to the patient continuously for a period of greater than orequal to about four, 12 or 24 hours. The light applicator can also havean effective treatment area of greater than or equal to 10 cm², orgreater than or equal to 100 cm².

In still further embodiments, the light applicator can include twosurface areas for treating two areas of the patient's skin. The twosurface areas can provide light of differing intensity or light ofdiffering wavelengths. Systems of, or used by, the invention may alsoinclude at least one sensor provided in communication with a controllerfor measuring at least one of skin temperature, oxygen saturation intissue being treated, and photosensitizer drug level. The controller canuse information provided by the sensor to turn on or off the power tothe light applicator or to vary the fluence provided by the lightapplicator. Where the light applicator includes two surface areas fortreating two areas of the patient's skin, at least one sensor canassociated with the treatment provided at each surface area.

Still further, the light applicator can also be integrated into agarment that is worn by the patient. The light applicator may be affixedto the garment, affixed with an adhesive, affixed by stitching, or, thegarment may consist essentially of the light applicator. The lightapplicator can further be configured to be affixed to the patient'sskin. For example, the light applicator might be fixed to the patient'sskin using an adhesive, or it may include a backing fixed to a back sideof the fiber optic cloth, the backing being larger than the fiber opticcloth and having adhesive on a skin facing surface area for affixing thelight applicator to a patient's skin.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood from the following detaileddescription taken in conjunction with the accompanying drawings:

FIG. 1 illustrates a flow of method steps according to one embodiment ofthe invention providing continuous low irradiance photodynamic therapy;

FIG. 2 illustrates a light applicator of the invention useful with themethod of FIG. 1;

FIG. 3 illustrates a portion of the light application of FIG. 2;

FIGS. 4A and 4B illustrate variations on the configuration of the lightapplicator of FIG. 2;

FIG. 5 illustrates two further applications of the light applicator ofFIG. 2; and

FIG. 6 illustrates a further application of the light applicator of FIG.2.

DETAILED DESCRIPTION OF THE INVENTION

The present invention enables the use of continuous low irradiancephotodynamic therapy. Using the methods and systems described herein, itmay be possible to treat patients outside of the clinic, in a way thatcan be home based and unobtrusive to the patient. The methods andsystems of the invention are most likely to be applicable to patientswith cutaneous, subcutaneous, mucosal, intra-articular, and hematologicdiseases that may be amenable to treatment using photodynamic therapy.These include patients having skin and soft-tissue cancers, acne, breastcancer, and in particular, patients having metastatic lesions throughthe dermis/epidermis and subcutaneous and breast fat and certainlymphomas.

A method 10 according to one embodiment of the invention is illustratedin FIG. 1. According to the method 10, a photosensitizer is applied tothe patient to be treated 12. A variety of photosensitizers are known inthe art and can be used with the invention. The photosensitizer can beapplied topically to the treatment site, post-operatively,intra-muscularly, intra-articularly, intra-veinously, or orally at aspecified time or times prior or during treatment. Conventionalphotosensitizers may be used (including those described in the documentsincorporated by reference in the Background), or others may be developedspecifically for use with the invention.

In one exemplary embodiment, the photosensitizer is 5-aminolevulinicacid (ALA). 5-Aminolevulinic acid, also known as 5-aminolaevulinic acid,delta-aminolevulinic acid, delta-aminolaevulinic acid, or5-amino4-oxopentanoic acid, is an intermediate in the pathway to theproduction of the photosensitizer, proptoporphyrin IX (PpIX). In thepresent invention, 5-Aminolevulinic acid can be used as a salt, such asthe hydrochloride salt. 5-Aminolevulinic acid can also be used in apharmacologically equivalent form, such as an amide or ester. Examplesof precursors and products of 5-aminolevulinic acid andpharmacologically equivalent forms of 5-aminolevulinic acid that can beused in the present invention are described in J. Kloek et al.,“Prodrugs of 5-Aminolevulinic Acid for Photodynamic Therapy,”Photochemistry and Photobiology, Vol. 64 No. 6, pp. 994-1000 (December1996); WO 95/07077, published Mar. 16, 1995, entitledPhotochemotherapeutic Compositions Containing 5-Aminolevulinic Acid; Q.Peng et al., “Build-Up of EsterifiedAminolevulinic-Acid-Derivative-Induced Porphyrin Fluorescence in NormalMouse Skin,” Journal of Photochemistry and Photobiology B: Biology, Vol.34, No. 1, (June 1996); and WO 94/06424, Mar. 31, 1994, entitledTranscutaneous In Vivo Activation of Photosensitive Agents in Blood.These references are incorporated herein in their entirety. The term“ALA” refers to all of the above-referenced compounds as describedherein.

In one preferred embodiment, ALA is provided oral administration. Oralapplication of ALA in the context of breast cancer is described, forexample, in D. P. Ladner et al., “Photodynamic diagnosis of breasttumours after oral application of aminolevulinic acid,” British Journalof Cancer, Vol. 84, pp. 33-37 (2001), which is incorporated herein inits entirety. By providing the photosynthesizer in an orallyadministered form, treatments may more readily be provided on anout-patient or even an at-home basis.

In further embodiments, Photofrin (available from Axcan Pharma Ltd. ofIreland) can be intravenously administered as the photosensitizingagent. This drug has been FDA approved for PDT treatment ofendobronchial lung and esophageal cancers, and also has been approvedfor the treatment of bladder cancer in Canada. Due to the Photofrin'sextended half-life, the level of drug in the tissue remains stable forover 36 hours after intravenous administration. In addition, there aremore than fifteen photosensitizers described, for example, in the UnitedStates patents and patent applications that could find suitable use withthe present invention.

Method 10 further includes applying a conformable, skin-facing lightapplicator to the patient 14. The applicator should be conformable sothat its shape can adapt to the contours of the patient's skin and sothat the applicator is comfortable for the patient over an extendedperiod of application. The applicator must be skin facing in the sensethat it must irradiate the skin. The applicator will preferably be incontact with the patient's skin, or very close to the patient's skin, inuse. Specific examples of fiber optic cloth based applicators aredescribed in greater detail below.

Treatment of the patient by providing continuous low-irradiancephotodynamic therapy 16 is further included in method 10. Low irradiancetreatment generally provides a treatment level that is sufficient toinitiate a photodynamic effect, which can then be continued over adesired period of time to achieve the desired treatment level in thetarget tissue, without causing damage to surrounding tissue. This isparticularly the case where the surrounding tissue has already beendamaged or is susceptible to damage due to prior treatments. In onepreferred embodiment, low irradiance treatment includes providing alight intensity to the skin that is less than or equal to about 5mW/cm², or more preferably, between about 0.25 and 3 mW/cm². In order toachieve the desired light fluence in the target tissue, the applicatoris preferably applied in dosages of greater than about one hour, greaterthan about four hours, greater than about 12 hours, or greater than orequal to about 24 hours. Treatments may also be fractionated—, i.e.,multiple doses of, say, 12 hours each, may be provided. Still further,the light source, or segments of the light source, can be independentlyturned on and off automatically (for example, in response to readingsfrom a sensor on the patient that indicates that tissue in a particulararea is oxygen depleted).

In one exemplary embodiment illustrated in FIG. 2, a light applicator100 is formed from a fiber optic cloth 102 having a number of opticalfibers 104 that “leak” light out of at least one surface of the cloth ata known, and controllable, rate. The optical fibers 104 are gathered atone end to form a fiber optic cable 106 leading to a connector 108 wherea light source 110 can be applied to power the fiber optic cloth 102. Inanother embodiment, the light applicator can be formed of an array oflight emitting diodes fixed to a conformable substrate such as a plasticfilm or a cloth.

Fiber optic cloth 102 can be provided on a backing layer 112 tofacilitate its application to a patient's skin. The backing layer 112can be, for example, a film or coating that can be applied to a backside of the fiber optic cloth, or it could be a portion of the patient'sclothing to which a transparent layer 114 has been applied to form apocket having a transparent window 116 that can be directed toward thepatient's skin.

Light source 110 is mounted to a holder 118 that, in turn, is mounted tothe backing layer 112. In this way, a desired connection between thelight source 110 and the connector 108 can be maintained even if thelight applicator 100 is jostled or moved. Wiring 128 for the lightsource 110 can lead to an electrical connector 120, and a cable 122 canbe attached to the connector so that the light source can beelectrically connected to a source of power and any desired controlelectronics that can be provided “off-board.” Alternatively, a powersource, such as a battery, can be provided on the backing layer 112 forconnection to wiring 118 to power the light source.

Light source 110 can be a commercially available laser or LED lightsource, and preferably emits light in a wavelength in the visible range.More preferably, the light source can produce light having a wavelengthbetween about 300 and 700 nm, still more preferably, the light sourcecan produce light having a wavelength between about 550 and 650 nm. Inone embodiment, the light source can be a laser producing light having awavelength of about 630 nm, as such light sources are used in consumerelectronic applications and can be found in small, light weight, lowcost packages.

Further details of one embodiment of fiber optic cloth 102 can be seenin FIG. 3, which shows a portion of one optical fiber 130 from cloth102. The optical fiber 130 can include a light transmitting core 132 ofa suitable transparent material and an outer sheath or cladding 134 of asecond transparent material typically having a lower index of refractionthan the core material to regulate the amount of light 136 that escapesfrom the fiber 130 along its length. In the illustrated embodiment, theoptical fiber 130 is woven about fill threads 138 to create a cloth thatis comfortable and conformable, and also to create bends in the fiberthat allow light to escape the fiber. The amount of light emitted by thecloth will depend on the depth and frequency of these bends, and alsoupon the nature of the light input 140 to the fiber. Fiber optic clothhaving this construction can be seen in U.S. Pat. Nos. 6,030,089;5,568,964; 4,885,663; 4,907,132; and 5,042,900; each of which is herebyincorporated by reference.

Alternatively, optical fiber 130 could rely on disruptions on theexternal surface of the optical fibers, by scratching, etching orotherwise causing mechanical, chemical or other deformations at discretelocations along their lengths. Examples of such fibers and their use areprovided in U.S. Pat. Nos. 4,885,663 and 4,761,047, which are herebyincorporated by reference. One possible advantage of this approach toforming the fiber optic cloth 102 is that the fibers can readily bedesigned to emit light on only one side, i.e., the patient facing side,so that power supplied to the applicator will more efficiently beapplied to treatment.

It is also desirable for the light applicator to cover a sufficient areato provide the desired treatment. In one embodiment, the applicator hasan effective treatment area (i.e., the surface area that provides lightdirected towards the patient's skin) of greater than equal to about 10cm². In a further embodiment, the applicator has an effective treatmentarea of greater than or equal to about 100 cm², or in anotherembodiment, an effective treatment area of about 100 cm².

FIGS. 4A and 4B illustrate two further embodiments of a light applicator150, 170, respectively, that can be used with the present invention.Light applicator 150 applies fiber optic cloth 102 to an article ofclothing 152 that is intended to be worn up against the patient's skin154 so that light 156 emanating from the fiber optic cloth 102. In theillustrated embodiment, an attachment element 158 attaches the fiberoptic cloth 102 to the clothing 152. In one embodiment, the attachmentelement 158 could be a film or backing that is attached to the fiberoptic cloth 102 and stitched into the clothing. In another embodiment,attachment element 158 could be a layer of pressure sensitive adhesivethat could applied directly to the fiber optic cloth 102 or to a backingon the cloth. A person of ordinary skill in the art will recognize thata number of variations on these described configurations can be used inkeeping with the spirit of the invention.

Light applicator 170 is configured in the form of a “patch” that can beapplied directly to the skin. In this exemplary embodiment, a backing172 is provided that is larger than the fiber optic cloth 102 so that anadhesive can be applied on the margin of the backing that faces theskin. In this way, adhesive need not be applied to the skin facingportion of fiber optic cloth 102 as the optical qualities of the clothmay be impacted by the application of such an adhesive. Light is fed tofiber optic cloth 102 in this embodiment by a fiber optic cable 106,which can be connected using connector 108 to a light source 110, whichin turn can be powered by an “off-board” energy source if desired usingwire 128.

FIG. 5 illustrates the application of two light applicators to a patient200. In a first application, a fiber optic cloth 102 is built into apatient's clothing, particularly brassiere 202, using stitching 204. Inthis application, connector 120 allows wire 122 to run to a controller206 mounted on the patient's belt 208. Controller 206 may include anenergy source such as a battery. Controller 206 may also includeregulating electronics to process the energy for consumption by thelight applicator. Still further, controller 206 may include on/offand/or attenuation controls to allow a particular power level to be setfor energy delivery to the light application. Still further, controller206 may include a processor that allows for a course of treatment to be“programmed”—setting, for example, particular power levels to beprovided at particular times and particular durations for the lightapplicator.

The second application illustrated in FIG. 5 provides a light applicatorin the form of a wrist band 220. The wristband may consist entirely offiber optic cloth, or it may have a skin facing fiber optic cloth with afurther fabric covering, or other combinations as may be known to theperson of ordinary skill. In this example, a controller 222, similar tocontroller 206, is mounted directly to the item of clothing (here thewristband).

The invention may be applied to treat a variety of patients, includingthose having cutaneous, subcutaneous, mucosal, intra-articular andhematologic diseases that may be amenable to treatment using PDT. Thesepatients include, but are not limited to, skin and soft-tissue cancerpatients, acne patients, patients with photodamaged skin (such as thosewith actinic keratoses, dyspigmentation, solar elastosis and includingthose with wrinkles), patients with breast cancer, in particularmetastatic lesions through the dermis/epidermis and subcutaneous andbreast fat and certain lymphomas.

One indication that may be particularly appropriate for application ofthe present invention is the eradication of external lesions where,currently, multiple high dose treatments are completed for conventionalPDT to effect treatment. It is possible that continuous low irradiancetreatment such as that provided by the present invention will bepreferable for long term survival. This strategy eliminates problemsassociated with high dose treatments, including depletion of tissueoxygen (O2), which is converted to effect tumor kill. The use ofcontinuous low irradiance therapy for external lesions will be increasedif patients are minimally inconvenienced during their long termtreatment. This suggests that a wearable system may be optimal, wherebythe patient can complete normal activities of daily living duringtreatment. Alternatively or in addition, long term treatment can beachieved during the night while sleeping. The present invention canfacilitate long term treatment by providing suitable light exposure inan unobtrusive manner. Patient inconvenience for repeated visits, andexcessive thermal damage caused by the high laser powers used. As aresult of the disadvantages of conventional PDT, many such lesions arenot treated using PDT. A further condition that may be currentlyundertreated using PDT is the erosion of breast cancer lesions throughthe dermis and epidermis. This indication, known by clinicians as “fieldof fire” should be optimal for continuous low irradiance PDT treatment.

The light applicator of the invention can be woven or formed into theappropriate garment such as a ski mask for facial tumors or shirt forchest wall cutaneous metastases from breast cancer or socks for diabeticfoot and leg ulcers. Construction of the light applicator can alsoinclude the ability to control areas within the garment which receivelight of differing intensities or specific wavelengths of light indifferent portions of the garment or garments, for example byoverlapping or weaving side by side fiber optic fibers that are poweredby different light sources and/or control electronics. For example, inthe treatment of mammary Paget's disease, a fiber-optic brassiere couldbe fashioned in which a particular wavelength of light emanates over theareolas and a different wavelength of light over the tail of the breastand no light emitted on the posterior portion of the garment. In thetreatment of psoriatic arthritis, fiber-optic gloves could be fashionedwhich emit a higher intensity, short wavelength light on the dorsalaspect of the joint where the skin is thinner and a longer wavelengthlight on the volar/plantar aspect where skin is thicker and deeperpenetration is necessary.

Continuous therapy, outside the physician's office or hospital can alsobe enabled by such a wearable light-emitting garment. In diseases suchas cutaneous T-cell lymphoma, where patients undergo extra-corporialphotophoresis, the risks of the blood circuit, infection, blood loss,thermal damage to blood elements, pain and need to be in a hemodialysisunit for the treatment may be eliminated. By simply wearing a shirt andpants garment, 90% of the cutaneous surface, with its vast vascularplexuses will enable these lymphoma patients non-invasive, high-qualityof life therapy. Wearable chronic therapy PDT devices will be useful forall external and subcutaneous medical conditions treatable via currentand future PDT applications. This includes skin cancers, and other skinconditions, including acne, leg ulcers and proliferative diseases suchas actinic keratoses, psoriasis, etc. Due to deeper penetration oflonger wavelength light, subcutaneous diseases, such as cancersmetastatic to skin/subcutis can be treated, as well as intra-articulardiseases in small joints of the hands—psoriatic and rheumatoidarthritis.

By way of example, arthritis and intra-articular diseases in the smalljoints of the hands could be treated using the glove 240 illustrated inFIG. 6. In this example, a number of light applicators 242 (illustratedin the Figure as black regions) could be integrated into the glove 240so that the light applicators apply light to the desired joints, such asthe distal and proximal interphalangeal joints and metacarpal-phalangealjoint an embodiment for treating arthritis. The palmar surface couldalso be illuminated for palmoplantar psoriasis. In a further elaborationof this embodiment, fluence could be moderated to each site, or eachsite turned on and off independently, by a controller located on theglove or connected to it by an appropriate cable or cables (not shown).

In a further specific application of the invention, continuous lowirradiance photodynamic therapy can be effective for human subjects withchest wall recurrences of breast cancer and skin metastases of malignantmelanoma that have failed conventional ionizing radiation therapy.Chest-wall progression of breast cancer is disproportionately seen amongunderserved populations and re-treatment of previously of irradiatedskin often is problematic in all socio-economic groups. Conventionalphotodynamic therapy is reported to have complete response rates of64-89% for chest-wall progression of breast cancer in patients who havefailed radiation, chemotherapy and surgical resection. PDT has notentered mainstream cancer care due to excessive morbidity and thecomplexity of administering the therapy. Virtually 100% of patientsdevelop skin necrosis and large areas of full-thickness skin ulceration,requiring inpatient management, pain and protracted wound care. Thesefactors limit the size of the treatment field and few Centers offer thistherapy. In contrast to conventional photodynamic therapy, which caninduce non-specific tissue necrosis, continuous low irradiancephotodynamic therapy of the invention may avoid necrosis and theresulting full-thickness skin ulceration. Large cutaneous surfaces, suchas the entire chest-wall for breast cancer could then be treated withthe invention.

The invention being thus disclosed and illustrative embodiments depictedherein, further variations and modifications of the invention will occurto those skilled in the art. All such variations and modifications areconsidered to be within the scope of the invention, as defined by theclaims appended hereto and equivalents thereof.

What is claimed is: 1-46. (canceled)
 47. A system for photodynamictherapy comprising: a light delivery device that delivers illuminationnecessary to perform photodynamic therapy, the light delivery deviceincludes a skin facing area for illumination of a selected region of abody for photodynamic therapy; a light source coupled to the lightdelivery device to provide illumination to the light delivery device;and a controller having a processor programmed to control theillumination delivered by the applicator such that the applicatordelivers less than or equal to 3 mW/cm² through its skin facing area forillumination for a time period sufficient to activate a photosensitizer.48. The system of claim 47, wherein the processor is programmed tocontrol the illumination delivered by the applicator such that theillumination is delivered for a time period of at least 4 hours.
 49. Thesystem of claim 47, wherein the processor is programmed to control theillumination delivered by the applicator such that the illumination isdelivered for a time period of at least 12 hours.
 50. The system ofclaim 47, wherein the processor is programmed to control theillumination delivered by the applicator such that the illumination isdelivered for a time period of at least 24 hours.
 51. The system ofclaim 47, wherein the processor is programmed to control theillumination delivered by the applicator such that an illumination doseis fractionated into multiple doses.
 52. The system of claim 47, whereinthe skin facing area is at least 10 cm².
 53. The system of claim 47,wherein the skin facing area is at least 100 cm².
 54. The system ofclaim 47, wherein the skin facing area includes optical fiber havingdisruptions in a skin facing direction, the disruptions being arrangedto cause light to be emitted in the skin facing direction.
 55. Thesystem of claim 54, wherein the disruptions are formed by etching. 56.The system of claim 47, further comprising a photosensitizer foractivation by the light delivery device.
 57. A method for providingcontinuous low irradiance photodynamic therapy to a patient, comprising:applying a skin facing light applicator to the patient; and providing alight intensity of less than or equal to 3 mW/cm² through the lightapplicator to activate a photosensitizer and thereby treat the patient.58. The method of claim 57, wherein the light is delivered for a timeperiod of at least 4 hours.
 59. The method of claim 57, wherein thelight is delivered for a time period of at least 12 hours.
 60. Themethod of claim 57, wherein the light is delivered for a time period ofat least 24 hours.
 61. The method of claim 57, wherein the light isdelivered such that an illumination dose is fractionated into multipledoses.
 62. The method of claim 57, wherein the light applicator deliverslight through a skin facing area that is at least 10 cm².
 63. The methodof claim 57, wherein the light applicator delivers light through a skinfacing area that is at least 100 cm².
 64. A system for treating apatient using light therapy comprising: a light delivery device thatdelivers illumination necessary to perform photodynamic therapy, thelight delivery device being in the form of a facial mask and including askin facing area for illumination of a selected region of a patient'sfacial skin for therapy; a light source coupled to the light deliverydevice to provide the necessary illumination to the light deliverydevice; and a controller having a processor programmed to control theillumination delivered by the applicator such that the applicatordelivers less than or equal to 3 mW/cm² through its skin facing area forillumination of the selected region of the patient's facial skin fortherapy.
 65. The system of claim 64, wherein the processor is programmedto control the illumination delivered by the applicator such that theillumination is delivered for a time period of at least 4 hours.
 66. Thesystem of claim 64, wherein the processor is programmed to control theillumination delivered by the applicator such that the illumination isdelivered for a time period of at least 12 hours.
 67. The system ofclaim 64, wherein the processor is programmed to control theillumination delivered by the applicator such that the illumination isdelivered for a time period of at least 24 hours.
 68. The system ofclaim 64, wherein the processor is programmed to control theillumination delivered by the applicator such that an illumination doseis fractionated into multiple doses.
 69. The system of claim 64, whereinthe skin facing area includes optical fiber having disruptions in a skinfacing direction, the disruptions being arranged to cause light to beemitted in the skin facing direction.
 70. The system of claim 69,wherein the disruptions are formed by etching.
 71. The system of claim64, further comprising a photosensitizer for activation by the lightdelivery device.
 72. A method for providing light therapy to a patient,comprising: providing a light applicator in the form of a facial mask;applying the facial mask to the patient's face so that a light applyingsurface of the light applicator faces a selected region of the patient'sfacial skin; and providing a light intensity of less than or equal to 3mW/cm² through the light applicator to thereby treat the selected regionof the patient's skin.
 73. The method of claim 72, wherein the light isdelivered for a time period of at least 4 hours.
 74. The method of claim72, wherein the light is delivered for a time period of at least 12hours.
 75. The method of claim 72, wherein the light is delivered for atime period of at least 24 hours.
 76. The method of claim 72, whereinthe light is delivered such that an illumination dose is fractionatedinto multiple doses.